Bicyclic compounds containing a pyrimidine skeleton in the structure thereof are disclosed as an antipsychotic agent in WO97/47601; as a metabotropic glutamate receptor 1 (mGluR1) antagonist in WO2001/32632; as a glycogen synthase kinase 3 (GSK3) inhibitor in WO2001/44246; as a protein kinase inhibitor in WO2002/22601, WO2002/22602, WO2002/22604, WO2002/22606, WO2002/22607, WO2002/50065 and WO2002/62789; as a modulator of CC chemokine receptor 4 (CCR4) function in WO2002/30358 and US Published Patent Application No. 2003/0173524; and as a phosphodiesterase 7 (PDE7) inhibitor in WO2002/87513, respectively.
TARC was found as a T cell chemotactic factor [Journal of Biological Chemistry, vol. 271, p. 21514 (1996)], and MDC was found as a monocyte chemotactic factor [Journal of Experimental Medicine, vol. 185, p. 1595 (1997)]. Particularly, TARC is assumed to be involved in allergic diseases, since it is formed from a monocyte stimulated by Th2 cytokine [Journal of Biological Chemistry, vol. 271, p. 21514 (1996)]. Further analyses have shown that TARC and MDC are CCR4 ligands [Journal of Biological Chemistry, vol. 272, p. 15036 (1997); and Journal of Biological Chemistry, vol. 273, p. 1764 (1998)].
CCR4 has been cloned as a receptor expressed in T cells and thymocytes [Biochemical and Biophysical Research Communications, vol. 218, p. 337 (1996)], and further investigation shave reported that CCR4 is mainly expressed in “Th2” T cells [Journal of Experimental Medicine, vol. 187, p. 875 (1998); and Journal of Immunology, vol. 161, p. 5027 (1998)].